G IS.’i'iCo 
^ c\  Co  nJ 


A Review  of  Literature  on  the  Estimation  of  Alkaloids 
for  the  Year  1904. 


By  W.  A.  Puckner. 


Two  interesting*  contributions,  discussing  in  a general  way  the 
methods  of  estimating  alkaloids  in  drugs  were  published  in  1904. 
One,  by  E.  Beuttner1  discussed  a series  of  publications  by  Panchaud 
on  the  valuation  of  Drugs,  the  work  having  been  done  at  the  request 
of  the  Swiss  Pharmacopoeia  Commission,  the  other,  by  G.  Fromme2 
reviews  both  Panchaud’s  and  Beuttner’s  conclusions. 

Panchaud  ?s  publications  were  devoted  to  a general  discussion  of 
the  Keller  method  which  he  considers  far  superior  to  all  others,  and 
to  its  application,  with  proposed  modifications,  to  the  various 
alkaloidal  drugs. 

Beuttner  agrees  with  Panchaud  that  the  water  added  in  the 
Keller  method,  to  cause  the  drug  to  separate  in  masses,  may  be  the 
cause  of  an  error  because  alkaloids  are  not  entirely  insoluble  in 
water  or  in  water  containing  an  alkali,  but  that  this  error  is  not 
large  unless  an  unnecessarily  large  volume  is  added. 

While  Panchaud  recommends  that,  in  the  examination  of  tinctures 
and  fluidextracts,  they  be  distributed  over  sand  and  dried,  Beuttner 
does  not  approve  of  this  because  the  product  is  hygroscopic  and  can 
therefore  not  be  transferred  quantitatively  and  because  emulsions 
are  sometimes  formed.  Instead  he  suggests  to  concentrate  the  tinc- 
ture or  fluidextract  in  a flask  to  a small  volume  and  then  to  add 
very  little  water,  the  required  volume  of  ether  or  ether-chloroform 


1 Schweizerische  Wochenschrift,  1904,  42,  57. 
- Geschafts-Bericht,  1904,  Caesar  & Loretz. 


9 


mixture  and  then  1—2  Gm.  ammonia  water.  By  reducing  the  am- 
monia water  added,  the  total  aqueous  fluid  need  not  be  more  than 
6 — 12  Gm.,  which  is  less  than  in  the  “sand  method.” 

Beuttner  agrees  with  Panchaud  that  ammonium  hydroxide  should 
be  given  the  preference  over  sodium  hydroxide  in  liberating  the  alka- 
loid, but  notes  that  usually  the  amount  used  is  excessive  and  says 
that  1—2  Gm.  of  ten  percent  ammonia  water  is  quite  sufficient. 

Fromme  discusses  the  work  of  Panchaud  and  Beuttner  in  con- 
siderable detail  and  concludes: 

While  a very  fine  powder  is  more  easily  and  more  quickly 
extracted,  most  drug  are  readily  exhausted  when  not  so  finely 
powdered  and,  since  it  is  not  an  easy  matter  to  reduce  certain  drugs 
to  so  fine  a powder  it  should  be  -directed  only  when  there  is  real 
need  for  it  as  in  golden  seal. 

Air  dried  drug  is  to  be  preferred  over  that  dried  at  100  degrees 
C.  and  if  desired,  moisture  may  be  determined  in  a separate  portion. 

Whether  ether,  chloroform  or  a mixture  of  the  two  is  to  be  pre- 
ferred depends  on  the  nature  of  the  alkaloid  to  be  extracted.  If  the 
alkaloid  is  sufficiently  soluble  in  ether  then  this  should  be  used  since 
it  is  less  liable  to  form  emulsions;  in  ipecac  it  must  be  used  since  it 
rejects  an  inert  alkaloid. 

Generally  ammonium  hydroxide  is  to  be  used  to  set  free  the 
alkaloid.  Exceptions  are  drugs  containing  volatile  alkaloids  where 
the  ammonia  dissolved  by  the  ethereal  solvent  can  not  be  wholly 
expelled  by  heat  and  where  sodium  hydroxide  is  to  be  preferred.  As 
a result  of  many  trials  he  also  uses  it  in  cinchona  assays. 

With  few  exceptions  one-half  to  one  hour’s  digestion  of  the  drug 
with  the  alkali  and  solvent  is  sufficient  if  the  mixture  is  shaken 
frequently. 

Usually  no  difficulty  is  experienced  in  decanting  a clear  aliquot 
portion  of  the  solvent  and  hence  the  addition  of  water  is  superfluous ; 
when  the  alkaloid  to  be  estimated  is  soluble  in  water  then  it  of 
course  is  objectionable.  Paper  filters  are  not  permissible  when  an 
aliquot  portion  is  to  be  taken:  they  may  cause  an  error  as  high  as 
10  percent.  Cotton  may  be  used : if  the  ethereal  fluid  is  not  per- 
fectly clear  it  may  be  shaken  with  1 Cc.  water  and  this  drawn  off. 

In  a general  way  Panchaud’s  “simplified  method”  which  requires 


no  separatory  funnel  and  no  volumetric  alkali,  is  to  be  commended. 
The  method  directs  the  drug  to  be  shaken  with  the  volatile  solvent, 
then  the  required  alkali  added  and  the  mixture  shaken  for  a specified 
time.  After  standing  a rest  for  a time  as  mueh  as  possible  of  the 
clear  supernatant  fluid  is  poured  into  a conical  flask,  weighed,  a 
portion  of  the  solvent  and  with  it  all  the  ammonia,  is  distilled  off 
and  in  the  remaining  liquid,  adding  hematoxylin,  alcohol  and,  to- 
ward the  end,  water,  the  alkaloid  is  determined  by  titration  with 
tenth-normal  hydrochloric  acid. 

Fromme  questions  the  advantage  of  doing  away  with  the  volu- 
metric alkali:  often  an  excess  of  alkali  is  added  accidentally  and 
then  a residual  titration  must  be  resorted  to.  He  also  suggests  the 
substitution  of  tenth-normal  volumetric  ammonium  hydroxide  and 
explains  the  desirability  of  combining  a gravimetric  determination 
with  the  titration  as  a check  on  the  identity  of  the  alkaloid. 

Aconite.  While  G.  Fromme3  found  that  considerable  care 
must  be  exercised  to  completely  remove  the  volatile  alkaline  am- 
monium derivatives  before  titrating  the  alkaloidal  residue  obtained 
in  the  examination  of  aconite  root,  Beuttner4  has  been  unable  to- 
demonstrate  the  presence  of  such  volatile  bases.  The  method  which 
he  proposes  and  which  assumes  the  absence  of  these  volatile  bases, 
gave  results  which  agreed  well  with  those  obtained  by  the  Keller 
method  were  ether  was  used  as  a solvent  and  the  alkaloidal  residue 
either  weighed  or  titrated. 

For  tincture  of  aconite  root  he  directs:  60  Gm.  are  evaporated 
in  a beaker,  with  frequent  stirring,  to  10  Gm.  and  poured  into  a 
tared  vial.  To  the  beaker  one  drop  ammonia  water  is  added  and 
it  is  then  rinsed  with  ether  and  this  added  to  the  contents  of  the 
vial  until  it  contains  60  Gm.  ether.  Then  1 Gm.  ammonia  water  is 
added,  the  vial  stoppered  and  shaken  frequently  during  15  minutes. 
After  standing  at  rest  for  15  minutes,  50  Gm.  are  decanted  through 
a pledget  of  cotton  into  a 200  Cc.  flask.  The  ether  is  evaporated 
(distilled)  until  about  10  Gm.  remain,  then  5 Cc.  absolute  alcohol, 
30  Cc.  ether  and  three  drops  hematoxylin  solution  added  and  tenth- 
normal  hydrochloric  acid  run  in  until  the  watery  layer  is  reddish- 


3 Caesar  & Loretz  Geschafts-Bericht,  1903. 

4 Schweizer.  Wochenschrift,  1904,  42,  74. 


4 


brown,  then  30  Cc.  water  added  and  the  titration  continued  until, 
after  shaking,  the  wratery  layer  is  lemon-yellow. 

The  Mydriatic  Drugs.  It  is  now  well  known  that  the 
mydriatic  drugs  quite  generally  contain  volatile  bases5  and  that  the 
varying  results  obtained  when  assaying  the  mydriatic  drugs,  parti- 
cularly henbane,  by  different  methods  were  due  to  the  retention  of 
varying  proportions  of  volatile  bases  in  the  residue  finally  titrated. 

Beuttner6 *  finds  that  when  ether  is  used  in  the  valuation  of  belladonna 
leaves,  and  precautions  are  taken  to  completely  expell  the  volatile 
bases  that  an  almost  pure  alkaloid  is  isolated  as  shown  by  weighing 
and  subsequently  titrating  the  alkaloidal  residue.  He  directs  to 
macerate  15  Gm.  pow’dered  belladonna  leaves  with  95  Gm.  dilute 
alcohol  for  24  hours;  50  Gm.  are  then  to  be  filtered  off  and  reduced 
in  a tared  dish  or  beaker  to  12  Gm.  When  cool,  sufficient  water  to 
make  15.2  Gm.  is  added  and  the  mixture  then  filtered.  Of  this 
filtrate  12  Gm.  are  shaken  with  60  Gm.  ether,  and  lGm.  ammonia  water 
during  15  minutes  and  then  put  aside  for  15  minutes.  Of  the  ethereal 
layer  50  Gm.,  considered  to  represent  5 Gm.  drug,  are  poured 
through  cotton  into  a dry  flask  and  the  ether  driven  off.  The 
residue  is  dissolved  in  5 Cc.  ether  and  brought  to  dryness  three 
times  and  then  titrated. 

Fromme  has  compared  Beuttner's  method  writh  his  own,  a modi- 
fication of  Keller’s  method  in  which  ether  is  used  as  solvent  and 
where  care  is  taken  to  expell  all  volatile  bases,  and  finds  that  both 
yield  good  results  and  that  in  each  the  weight  of  the  residue  agrees 
with  that  calculated  from  a titration. 

W.  K.  Forstberg8  compares  several  methods  proposed  for 
the  valuation  of  belladonna  leaves  and  prefers  the  fol- 
lowing: 20  Gm.  very  finely  powrdered  drug,  dried  at  100°  C., 
are  moistened  with  20  Cc.  20%  soda  solution  and  brought 
to  dryness  on  a water  bath.  The  dry  material  is  transferred  to  a 
vial,  90  Gm.  ether  and  30  Gm.  chloroform  are  added,  and  after 
standing  one-half  hour  10  Cc.  sodium  hydroxide  solution,  20%,  are 
added,  the  mixture  shaken  frequently  during  2 hours,  then  20  Cc. 


5 Merck’s  Bericlit,  1900,  p.  11 ; Fromme,  Caesar  & Loretz  Geschafts-Bericht, 

1901,  p.  62;  H.  Thoms,  Apotheker-Ztg.  18,  p.  389  (C.  1903,  2,  p.  215). 

« Schweiz.  IVocheiischrift,  32,  p.  101. 

s Pharm.  Post  38,  p.  2 (Chem.  Centrbl.  1905,  1,  p.  409). 


5 


water  added,  and  after  standing  at  rest  during  one  hour  60  Grn. 
poured  off.  One-fourth  of  the  ethereal  fluid  is  distilled  off,  the  re- 
mainder transferred  to  a separator,  the  flask  rinsed  with  three  por- 
tions of  ether,  5 Cc.  each,  and  shaken  with  20  Cc.  normal  (?  W.  A.  P.) 
hydrochloric  acid,  then  5 drops  of  eosin  solution  are  added  and  the 
excess  of  acid  determined  with  hundreth-normal  alkali. 

E.  Leger9  uses  magnesium  hydroxide  for  the  liberation  of  alka- 
loids in  drugs  because  ammonia  water  is  liable  to  contain  pyridin 
which  will  contaminate  the  extracted  alkaloids  and  can  only  be  re- 
moved if  the  alkaloids  are  dried  thoroughly  at  100°  C.  If  ammonia 
water  is  to  be  used  it  should  be  freed  from  pyridine  by  shaking  with 
chloroform.  For  belladonna  leaves  he  directs  to  mix  the  dry  powder 
with  magnesium  oxide  and  water.  After  10  hours  washed  ether,  i.  e. 
ether  free  from  alcohol  and  saturated  with  water,  is  added  and  the 
mixture  shaken  frequently  during  12  hours.  An  aliquot  part  of  the 
ether  solution  is  then  taken,  the  ether  distilled  off,  the  residue  dis- 
solved in  neutral  ether  and  titrated. 

Cinchona.  While  some  progress  has  been  made  in  the  valua- 
tion of  cinchona  in  that  the  difficulty  of  completely  extracting  the 
alkaloids  by  ether  or  ether  chloroform  in  presence  of  alkali  has  been 
more  fully  recognized  little  has  been  accomplished  toward  the  elabo- 
ration of  a ready  means  of  estimating  the  proportion  of  quinine  in 
the  total  alkaloids. 

G.  Fromme10  has  studied  Panchaud’s  method  and  compares  it 
with  the  method  proposed  by  himself.  Panchaud  directs  to  add  to 
3 Gm.  very  finely  powdered  drug  30  Gm.  chloroform  and  90  Gin. 
ether  then  after  10  minutes  3 Gm.  10%  ammonia  water  and  shakes 
frequently  for  one  hour.  After  standing  at  rest  during  five  minutes, 
100  Gm.  of  the  clear  ether-chloroform  solution  are  poured  off  and 
reduced  to  10  Gm.  by  destination.  To  the  residue  30  Cc.  ether,  10 
Cc.  alcohol,  hematoxylin  solution  and  10  Cc.  water  are  added  and 
then  titrated  with  tenth-normal  hydrochloric  acid,  further  30  Cc. 
water  being  added  toward  the  end  of  the  titration. 

Fromme’s  method  directs  to  heat  2.5  Gm.  fine  or  coarse  powder, 
2 Cc.  25%  hydrochloric  acid  and  20  Cc.  water,  contained  in  a 200 
Cc.  flask  for  10  minutes  on  a water  bath,  and  when  cold  to  add  50 


9 J.  Pharm.  Chim.  (6)  19,  p.  923  (Chem.  Centrlblt..  1904,  1,  p.  1461. 

10  Geschafts-Bericht  v.  Caesar  & Loretz,  1904,  p.  18. 


6 


Gin.  ether,  25  Gin.  chloroform  and  after  shaking  vigorously  for  a 
moment  to  render  alkaline  with  5 Cc.  15%  sodium  hydroxide  solution 
and  then  to  shake  the  mixture  continuously  and  vigorously  during 
10  minutes.  Then  3 Gm.  powdered  tragacanth  are  added,  the  mix- 
ture shaken  thoroughly  and  at  once  60  Gm.  of  the  clear  ether- 
chloroform  solution  filtered  off.  This  is  reduced  to  one-half  its  bulk. 
After  adding  20  Gm.  ether,  the  alkaloids  are  extracted  by  shaking 
successively  with  10  Cc.  tenth-normal  hydrochloric  acid,  10  and  10 
Cc.  water.  To  demonstrate  that  all  alkaloid  has  been  removed  the 
ethereal  liquid  is  extracted  with  5 cc.  tenth-normal  acid  and  one 
drop  of  this  tested  with  Mayer's  solution.  If  free  from  alkaloid  this 
extraction  is  rejected,  else  it  is  added  to  the  first  extraction  and  the 
ether  extracted  with  several  portions  of  water  and  this  also  added 
to  the  first  extraction.  The  excess  of  acid  is  then  determined  and 
from  the  difference  the  weight  of  alkaloid  calculated. 

A bark  by  Panchaud's  method  gave  4.499,  4.460,  4.864,  4.864, 
5.10,  4.250%.  By  Fromme’s  method  6.584,  6.773  and  6.448%  was 
indicated.  And  when  the  finished  titrations  were  rendered  distinctly 
acid,  extracted  with  ether  to  remove  resinous  matter,  then  made 
alkaline  with  ammonia  and  extracted  with  ether-chloroform,  the  sol- 
vent distilled  off,  the  residue  when  dried  and  weighed  indicated 
6.565,  6.5000  and  6.460%.  From  a series  of  comparative  estima- 
tions then  made  it  appears,  that  the  ether-chloroform,  although 
more  is  used  than  in  the  original  Keller  method,  does  not  extract 
the  alkaloids  quantitatively  and  that  the  direct  method  of  titration 
as  proposed  by  Panchaud  does  not  determine  the  true  alkalinity  of 
the  alkaloidal  solution. 

E.  Beuttner11  adapts  Panchaud's  method  to  the  preparations  of 
cinchona.  For  the  valuation  of  the  fluidextract  he  directs  to  place 
3 Gm.  fluidextract,  4 Gm.  alcohol,  6 Gm.  water  and  5 Gm.  sand  in 
a 200  Cc.  flask  and  to  heat  the  mixture  on  a water  bath  until  the 
contents  are  reduced  to  12  Gm.  When  cooled,  90  Gm.  ether  30  Gm. 
chloroform  and  1 Gm.  ammonia  water  are  added  and  the  mixture 
shaken  during  15  minutes.  After  then  standing  at  rest  during  15 
minutes,  100  Gm.  are  decanted  through  cotton  • and  brought  to 
dryness.  The  residue  is  dissolved  in  10  Cc.  absolute  alcohol,  10  Cc. 
water,  30  Cc.  ether,  3 drops  hematoxylin  solution  added  and  t>hen 


n Schweiz.  Wochenschrift  42,  p.  74. 


titrated  with  tenthnormal  hydrochloric  acid.  A drug  which  by 
Panchaud’s  method  assayed  6.8%,  yielded  a fluidextract  which  by 
this  method  assayed  6.74%.  In  the  light  of  Fromme’s  experiments  this 
agreement  may  be  because  the  exhaustion  of  the  drug  in  the  assay 
and  in  the  manufacture  of  the  fluidextract  was  equally  incomplete. 

E.  Leger12  reports  results  obtained  with  four  different  methods. 
In  1.  the  drug  is  shaken  for  12  hours  with  a mixture  of  alcohol, 
ether  and  ammonia  water,  in  2.  chloroform  and  ammonia  water, 
with  macaration  for  4 hours  is  directed;  in  3.  the  drug  is  treated 
with  magnesium  oxide,  solution  potassium  hydroxide  and  water, 
after  two  hours  transferred  to  a continuous  extractor  and  exhausted 
with  chloroform;  in  4.  six  Gin.  drug  are  macerated  for  1 hour  with 
6 Cc.  ammonia  water,  24  Cc.  alcohol  and  then  120  Cc.  ether  added 
and  macerated  with  frequent  shaking  during  6 hours.  Then  120  Cc., 
taken  to  represent  4.8  Gm.  drug,  are  filtered  off  and  distilled  to 
complete  dryness.  The  residue  is  dissolved  in  ] 2’  Cc.  of  a solution 
containing  1 Cc.  strong  hydrochloric  acid  in  14  Cc.  and  filtered  to 
remove  resinous  material.  Of  the  filtrate,  10  Cc.  are  rendered  alka- 
line and  extracted  with  chloroform.  After  distilling  off  the  chloro- 
form, the  residue  is  dried  at  100°  C.  and  weighed.  The  results  were: 
1)  7.44%,  2)  7.96%,  3)  7.4%  and  4)  8.36%. 

B.  M.  Overton13  also  published  some  comparative  estimations 
which  illustrate  the  difficulty  of  exhausting  cinchona. 

J.  Warin14  discusses  the  valuation  of  cinchona  by  precipitating 
the  alkaloids  as  cinchotannates  from  a hydrochloric  acid  extraction 
of  the  drug.  He  finds  that,  no  matter  whether  acetic  acid  or  sodium 
acetate  be  used,  the  precipitation  is  incomplete,  and  that  on  washing 
the  precipitate  a part  dissolves,  whether  the  water  contains  acetic 
acid  or  not.  Comparative  results  may  be  obtained  by  closely  follow- 
ing details.  He  prefers  first  to  estimate  the  alkaloids  and  then,  if 
needed,  the  tannin,  in  the  solution  from  which  the  alkaloid  was  re- 
moved. 

While,  as  stated  before,  methods  for  the  separation  of  quinine 
from  other  cinchona  alkaloids  are  still  far  from  satisfactory,  yet 
some  advance  is  made.  E.  Leger15  has  studied  the  details  of  Andre’s 


12  J.  Pharm.  Chim.  (6)  19,  p.  479  Chem.  Centralbl.  1904,  2,  p.  161. 

Merck’s  report,  1904,  13,  353. 

1*  J.  Pharm.  Chim.  (6)  19,  p.  233;  Chem.  Centrlbl.  1904,  1,  p.  1110. 
is  J.  Pharm.  Chim.  (6)  19,  pp.  281,  434;  Chem.  Centrlbl.  1904,  1,  pp.  1180, 
1624). 


8 


bromine-ammonia  test  for  quinine  and  finds  that  it  can  be  used  for 
quantitative  estimations  only  if  close  attention  be  paid  to  all  details, 
and  that  the  directions  contained  in  the  Italian  and  Swiss  pharma- 
copoeias are  faulty. 

E.  Leger* 1*5  has  also  studied  the  composition  of  the  precipitated 
tartrates  obtained  from  a mixture  of  cinchona  alkaloids.  He  elabo- 
rates a method  which,  while  complicated,  appears  to  yield  correct 
results. 

B.  H.  Paul17  and  D.  Howard18  discuss  the  B.  P.  ether  test  for 
cinchonine  and  cinchonidine  in  quinine  sulphate.  While  Paul  upholds 
the  ether  test,  Howard  prefers  the  test  of  the  French  Codex. 

N.  Matolesy19  gives  the  following  modification  of  the  ether  test  : 
Measure  50  Cc.  of  the  solution  of  the  quinine  salt  to  be  tested  into 
a 100  Cc.  cylinder,  render  alkaline  with  sodium  hydroxide  solution, 
add  20  Gm.  powdered  sodium  chloride  and  20.2  Cc.  absolute  ether. 
Shake  5 to  10  miputes,  pipette  10  Cc.  to  a tared  dish,  evaporate, 
dry  at  100°  C.  and  weigh.  The  salt  so  reduces  the  solubility  of  ether 
in  water  that  50  Cc.  of  water  dissolve  only  0.2  Cc. 

Coca.  For  the  valuation  of  coca  leaves  E.  Leger1  employs  a 
a method  practically  identical  with  that  given  for  belladonna  leaves. 
He  notes  that  the  alkaloids  can  not  be  determined  gravimetrically 
because  one  of  the  coca  alkaloids,  namely  hygrine,  is  volatile. 

Beuttner2  studied  Panchaud’s  method  for  the  valuation  of  coca 
leaves  and  found  it  unsatisfactory.  He  says  that  aparently  the 
leaves  contain  a basic  non-alkaloidal  body  which  can  not  be  com- 
pletely expelled  from  the  alkaloidal  residue  even  though  the  latter  is 
repeatedly  dissolved  in  ether  and  again  brought  to  dryness.  In  a 
method  for  the  examination  of  the  fluid  extract,  ether  is  used  to 
extract  the  alkaloids  and  the  alkaloids  are  finally  dried  at  100°  C. 
and  weighed. 

Goldenseal.  Froinme  found  when,  in  the  assay  of  goldenseal, 
an  excess  of  ammonia  water  is  added  to  the  acid  solution  containing* 
the  hydrastine  and  this  then  shaken  with  ether,  that  from  the 


16  J.  Pharm.  Chim.  (6)  19,  p.  427;  Chem.  Oentrlbl.  1904,  1,  1624. 

17  Chemist  & Druggist  1902,  2,  65,  428,  506. 

is  Chemist  & Druggist,  1904,  2,  pp.  65,  475,  556. 
is  Pharm.  Post  37,  p.  177;  Chem.  Centrlbl.  1904,  1,  p.  1299. 

1 J.  Pharm.  Chim.  (6),  19,  p.  1460. 

2 Schw.  Wochenschft.  42,  p.  105. 


9 


ethereal  solution,  at  first  perfectly  clear,  crystals  of  hydrastine  will 
soon  separate  out.  This  has  been  fully  confirmed  and  has  no  doubt 
often  been  the  cause  of  lack  of  concordance  in  the  results  of  hydra - 
-stine  estimations.  Fromme3  finds  that  20  parts  ether  for  1 part 
drug  is  sufficient  to  retain  the  alkaloid  in  solution  and  directs:  6 
Gin.  very  finely  powdered  goldenseal,  100  Gm.  ether,  20  Gm.  petro- 
leum ether  and  5 Gm.  10%  ammonia  water  are  shaken  frequently 
and  vigorously  for  one-half  hour,  and,  after  the  drug  has  settled, 
100  Gm.  decanted  through  cotton  into  a separator.  From  this  the 
alkaloid  is  extracted  with  30,  20,  10,  10  Cc.  one-half  percent  hydro- 
chloric acid.  The  acid  solution  is  then  made  alkaline  with  ammonia 
water  and  extracted  with  30,  20,  10,  10  Cc.  ether.  The  ether  is  dis- 
tilled off  and  the  residue  dried  to  constant  weight. 

Ipecac.  It  having  been  shown  that  when  ether  is  used  to 
extract  the  ipecac  alkaloids  the  psychotrine  is  not  taken  up,  this  sol- 
vent has  replaced  the  chloroform  or  ether-chloroform  formerly  used. 
On  the  other  hand  the  separate  estimation  of  emetine  and  cephae- 
line,  as  proposed  by  Paul  and  Cownley  has  not  been  generally 
adopted  or  found  successful.  Two  methods  have  appeared  during 
the  year:  One,  by  E.  Beuttner4  uses  ether  as  a solvent,  thus  reject- 
ing the  inert  alkaloid;  the  other,  by  E.  Leger5 6  uses  a mixture  of 
ether' and  chloroform  and  therefore  estimates  the  '‘total’’  alkaloids. 

Nux  Yomica.  E.  Leger0  gives  two  methods  for  the  estimation 
of  alkaloids  in  nux  vomica.  E.  Beuttner7  discussed  the  valuation  of 
nux  vomica  preparations.  Both  recommend  methods  based  on  that 
of  Keller  and  estimate  the  total  alkaloids,  i.  e.  do  not  distinguish 
between  strychnine  and  brucine. 

Opium.  Lyman  F.  Kebler8  presents  co-operative  work  on  opium 
assaying  undertaken  at  the  instance  of  tbe  Association  of  Official 
Agricultural  Chemists  and  in  which  participated : Blome,  Dohme, 
Doolittle,  Havenhill,  Kebler,  Lyons,  Mallinckrodt  Chemical  Works, 
Puckner,  Buddiman  and  Smith.  The  specimen  of  powdered  opium 


3 Geschafts-Bericht  v.  Caesar  & Loretz,  1904,  64. 

* Schwz.  Woehenschft.,  42,  p.  89. 

s J,  Pharm.  Chim.  (6),  19  p.  479;  Chem.  Centrbl.  1904,  2,  p.  160. 

6 J.  Pharm.  Chim.  (6)  19,  p.  479;  Chem.  Centrbl.  1904,  2,  p.  160. 

7 Schwz.  Wochenschrft.  42,  p.  77. 

8 Proc.  A.  Ph.  A.,  52,  p.  369. 


10 


sent  out  was  assayed  according  to  the  method  of  the  U.  S.  P.  1890, 
the  lime  method  of  the  U.  S.  P.  1880  and  the  B.  P.,  and  the  A.  B. 
Stevens  modification  of  the  lime  method.  The  morphine  obtained 
by  the  first  two  methods  was  then  tested  (1)  by  determining  the 
percent  of  loss  when  dried  at  110  degrees,  (2)  by  titrating  with 
tenth-normal  sulphuric  acid,  (3)  by  dissolving  in  a known  excess  of 
tenth-normal  alkali  and,  after  filtering  from  undissolved  matter, 
determining  the  amount  of  acid  in  excess  of  that  required  to  neutral- 
ize the  added  alkali,  and  (4)  by  determining  its  solubility  in  lime 
water.  The  results  showing  in  a striking  manner  the  unsatisfactory 
condition  of  morphiometry,  are  discouraging.  While  the  chemists 
co-operating  in  this  work,  presumably,  all  have  considerably  ex- 
perience in  the  testing  of  opium  their  results  are  widely  discordant, 
showing  a variation  of  more  than  five  percent  of  the  actual  mor- 
phine present  between  the  highest  and  lowest.  By  far  the  most  con- 
cordant results  were  obtained  by  Stevens'  method. 

G.  Fromme9  reports  regarding  the  nature  of  the  impurities  which 
are  thrown  down  when,  after  adding  ammonia  water  and  ether,  24 
hours  are  allowed  for  the  separation  of  the  morphine.  In  one  case 
he  found  a lithium  salt,  usually  it  was  calcium  meconate.  When 
following  the  short  Helfenberger  method  and  allowing  only  10 
minutes  for  the  separation,  then  morphine  was  obtained  which  left 
no  ash  on  ignition  and  when  titrated  required  exactly  the  theoretica- 
volume  of  volumetric  acid. 

P.  Schidrowitz10  published  a method  for  the  estimation  of 
morphine  in  opium  which  gives  results  agreeing  with  the  methods 
used  by  dealers  and  manufacturers  and  which  are  said  to  be  kept 
secret.  The  opium  is  moistened  with  water  and  after  15  minutes  is 
triturated  with  more  water  and  transferred  to  a flask  and  after  one 
hour  an  aliquot  part  is  filtered  off.  This  is  mixed  with  a solution 
of  sodium  salicylate,  filtered  and  in  an  aliquot  portion  of  this  filtrate 
the  morphine  precipitated  by  ammonia  water  in  presence  of  ether. 
Finally  the  morphine  is  estimated  with  volumetric  acid,  using  methyl- 
orange  as  indicator  in  the  titration  of  alkaloids;  this  would  seem 
a step  in  the  right  direction,  although  Kippenberger*  11  reports  the 
contrary.  Since  this  indicator  is  especially  sensitive  toward  weak 

9  Geschafts-Bericht  v.  Caesar  & Loretz.  1904,  55. 

10  The  Analyst  29,  p.  144;  Chem.  Centrbl.,  1904,  2,  p.  160. 

11  Z.  anal.  Chem.  39,  p.  201. 


11 


bases  a sharp  etid-point  should  be  obtained  provided  of  course  that 
its  rather  faint  color  is  not  obscured  by  the  colored  impurities  of 
the  morphine. 

C.  E.  Caspari12  has  worked  out  a method  of  estimating  codeine 
in  opium  which  promises  more  correct  results  that  those  obtained 
by  Van  der  Wielen’s  process,  this  being  the  only  previously  published 
method.  A specimen  of  powdered  Smyrna  opium  yielded  1.12%  and 
1.33%  codeine,  which  is  about  the  percent,  reported  in  the  opium 
specimens  examined  by  Van  der  Wielen  and  shows  the  statements 
found  in  text-book  to  the  effect  that  opium  contains  0.2  to  0.6% 
codeine,  to  be  wrong. 

Pomegranate.  Panchaud  modified  the  method  of  the  German 
Pharmacopoeia  by  substituting  ammonia  for  sodium  hydroxide,  by 
omitting  the  addition  of  water  before  taking  the  aliquot  portion,  by 
substituting  ether  for  the  mixture  of  ether  and  chloroform  and  by 
titrating  the  alkaloids  directly  after  a part  of  the  ether  has  been 
distilled  off.  He  directs  to  shake,  vigorously  and  frequently,  during 
one  hour  12  Gm.  powdered  bark  with  120  Gm.  ether  and  10  Cc. 
ammonia  water.  Then  100  Gm.  (10  Gm.  bark)  of  the  clear  ether 
solution  are  poured  off,  reduced  to  25  Gm.  by  destination  and 
titrated.  G.  Fromme13  approves  of  the  substitution  of  ether  for  the 
chloroform-ether  mixture  and  especially  the  omission  of  the  water 
since  the  alkaloids  are  quite  soluble  in  water.  Experiments  showed 
however  that  when  the  three-fourths  of  the  ether  is  distilled  off  that 
not  all  the  ammonia  is  expelled,  while  when  the  ether  is  all  distilled 
off,  much  alkaloid  was  lost,  the  alkaloids  of  pomegranate  being 
volatile.  Fromme’s  experiments  indicate  that  the  drug  contained 
some  salt  of  ammonium  or  similar  body  which  was  estimated  along 
with  the  alkaloid  when  sodium  hydroxide  was  used  to  set  free  the  alka- 
loid and  the  decanted  ether  solution. titrated  direuj|v.  If  on  the  other 
hand  the  ether  was  partly  distilled  off,  besideJBpe  ammonia  also 
some  alkaloid  appeared  to  pass  over.  Provisionally  he  proposes: 
To  12  Gm.  finely  powdered  drug,  contained  in  a 200  Cc.  vial,  120 
Gm.  ether  are  added  and  shaken  frequently  for  10  minutes.  Then 
10  Cc.  10%  sodium  hydroxide  are  added,  the  mixture  shaken 
thoroughly  and  frequently  during  one  hour  and  put  aside  10  minutes. 


12  Proc.  A.  Ph.  A.  52,  p.  386. 

13  Gesehafts-Bericht  v.  Caesar  & Loretz,  1904,  p 


As  much  as  possible  of  the  clear  ether  solution  is  poured  into  a 200 
Cc.  Erlenmeyer  flask,  weighed,  distilled  until  25  Gm.  remain,  then  10 
Gm.  water,  5 Gm.  alcohol  and  10  drops  hematoxylin  solution  added, 
then  tenth-normal  hydrochloric  acid  run  in  until  the  aqueous  layer 
is  reddish-brown,  and  well  shaken.  Next  30  Cc.  water  added  and  tit- 
rated with  frequent  shaking  until  the  aqueous  layer  is  lemon-j-ellow. 
1 Cc.  tenth-normal  hydrochloric  acid  = 0.01475  Gm.  alkaloid. 

Tobacco.  Several  contributions  treating  of  the  estimation  of 
nicotine  in  tobacco  appeared  during  1904.  In  part  these  estimations 
have  had  for  their  object  the  study  of  the  relation  between  alkaluidal 
content  and  quality  of  tobacco.  The  correct  estimation  of  nicotine 
has  also  become  important  because  of  the  large  use  of  tobacco 
extract  as  a constituent  of  sheep  dips.  Since  nicotine  is  one  of  the 
so-called  volatile  alkaloids  its  separation  from  ammonia  and  other 
volatile  bases  is  not  readily  accomplished  and  nicotine  estimations 
are  far  from  accurate. 

J.  Toth14  defends  his  method  against  criticisms  by  Pontag15. 

R.  Kissling10  liberates  the  alkaloid  with  sodium  hydroxide  and 
then  extracts  it  with  ether  in  a continous  extraction  apparatus.  To- 
expell  ammonia  he  distills  the  ether  slowly,  then  adds  to  the  residue 
a little  sodium  hydroxide,  drives  the  nicotine  over  by  steam  and 
titrates  the  alkaline  destillate  with  sulphuric  acid,  using  luteol  as 
indicator. 

Waldbott17  liberates  nicotine  in  tobacco  solutions  or  nicotine 
solutions  containing  ammonium  salt  by  means  of  sodium  bicarbon- 
ate and  extracts  the  alkaloid  with  chloroform.  Using  copper  sul- 
phate as  indicator,  he  adds  an  excess  of  acid  and  then  titrates  back 
with  alkali  until  a faint  cloud  is  produced.  The  error  due  to 
ammonia  liberated  by  the  sodium  bicarbonate  is  ordinarily  not  more 
than  0.2%. 

J.  A.  Emery1flmds  that  tabacco  extracts  sold  for  use  in  sheep 
dips  are  often  adulterated  with  pyridine.  This  is  estimated  as  nico- 
tine in  the  methods  of  analysis  usually  used  where  the  alkaloid  is 


14  Z.  f.  Unters.  Xahr.-Genussm.  7,  p.  151;  Chem.  Centrlbl.  1901,  1,  p.  840, 
is  Z.  f.  Unters.  Xahr.-Genussm.  6,  p.  673;  Chem.  Centrlbl.  1903,  2,  p.  729. 
ifi  Chem.  Ztg\  28,  p.  775;  Chem.  Centrlbl.  1904,  2,  p.  860. 

17  Pharm.  Centrh.  1904,  45,  p.  192;  Proc.  A.  Ph.  A.  52,  p.  949. 
is  J.  Am.  Chem.  Soc.  26,  p.  1113;  Chem.  Centrbl.  1904,  9,  p.  1347. 


13 


distilled  with  steam.  Emery  bases  an  estimation  of  nicotine  in  pre- 
sence of  pyridine  on  the  optical  inactivity  of  pyridine,  nicotine  being 
strongly  laevogyre.  First  the  total  volatile  bases  are  isolated  by 
steam  destination  in  the  usual  way  and  determined  by  titration 
with  acid  and  methyl-orange  as  indicator.  To  estimate  the  nicotine 
in  the  finished  titration,  its  polarisation  is  compared  with  that  of 
a solution  of  pure  nicotine  of  known  strength.  The  pyridine  is  then 
calculated  from  the  difference  between  the  titration  and  the  polariza- 
tion results. 


■* 


t 


